The proposed research studies were designed to explore the effects of in vitro and in vivo ethanol administration on brain synaptic membrane and on model lipid membrane organization and function. These studies will include an analysis of the effects of ethanol additions on the synaptic membrane glutamate receptor binding activity and coupling to the Na ion ionophore. Ethanol's interference with the ganglioside-induced modulation of receptor activity will be determined, as will the effect of ethanol on ganglioside binding to the purified receptor protein and to the synaptic membranes. The cellular adaptation with respect to glutamate receptors following prolonged exposure to ethanol will also be determined by measuring the total receptor content in synaptic membranes from chronically ethanol-treated rats. The effects of ethanol on lipid mobility at different depths in the membrane bilayer will be analyzed by means of EPR spectroscopic techniques. Such issues as the influence of the lipid composition and of the ionic environment of the membranes on ethanol's effects on lipid motion and protein rotational movement in model and biological membranes will be explored. Finally, studies will be undertaken to determine the processes involved in ethanol's stimulation of spontaneous neurotransmitter release. In particular the issue of stimulation of non-vesicular release of transmitters will be examined. Also the possibilitity that ethanol may affect Ca2 ion extrusion from the nerve terminal via interference with the Na ion-Ca2 ion exchange process in synaptic plasma membrane sacs will be determined.